Abstract
BACKGROUND: The pituitary gland, a central regulator of the hypothalamic-pituitary-gonadal (HPG) axis, plays a pivotal role in reproductive efficiency by precisely controlling the secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Chromatin accessibility enables physical interactions between promoters and chromatin-binding factors to drive the gene expression. Despite this mechanistic insight, the chromatin accessibility landscape of the sheep pituitary and its functional implications for reproductive traits remain largely unexplored. To address this knowledge gap, we performed an integrated multi-omics analysis of ATAC-seq and RNA-seq profiling of pituitary from sheep with divergent fecundity phenotypes. RESULTS: We identified 1,567 differential accessibility regions (DARs) and 768 differentially expressed genes (DEGs). Functional enrichment analysis revealed that the DEGs were significantly associated with key signaling pathways, including neuroactive ligand-receptor interactions, the cAMP signaling pathway, and the calcium signaling pathway, suggesting their critical roles in pituitary-regulated reproductive functions. Based on integrative analysis of ATAC-seq and RNA-seq, we revealed several potentially key genes involved in gonadotropin secretion, such as CMKLR1, TAFA1, and PPP1R17. Furthermore, we identified novel transcription factors (TFs), including NR4A2 and MEF2, which may influence pituitary hormone secretion by modulating chromatin accessibility and gene expression. CONCLUSIONS: This study systematically delineated the gene expression and chromatin accessibility of the pituitary and identified some key regulatory genes associated with gonadotropin secretion in sheep. Our integrated multi-omics analysis identifies critical molecular markers that may contribute to the genetic improvement of reproductive efficiency in ovine species.